Digital Cytopathology & Interactive Case Discussion Marilyn M. Bui, MD, PhD Senior Member & Scientific Director of Analytic Microscopy Core Section Head, Bone and Soft Tissue Pathology Program Leader, Anatomic Pathology Education Moffitt Cancer Center Professor & Director of Cytopathology Fellowship University of South Florida Morsani College of Medicine Tampa, FL. USA The mission of Moffitt Cancer Center is to contribute to the prevention and cure of cancer.
Disclosure There are no financial conflicts of interest. The talk represents my personal and professional opinion only. Member of Digital Pathology Association Board of Directors & executive committee, Editorial board member of Journal of Pathology Informatics, Member of Association of Pathology Informatics, CAP Digital Pathology Committee and contributing editor of CAP Digital Pathology Resource Guide 2014-2017, Chair of the CAP Expert Panel of the Quantitative Image Analysis project, Scientific Director of Analytic Microscopy Core at Moffitt Cancer Center, Leader of the departmental digital pathology working group, Member of the institutional Virtual Health Strategy working group, Patent applications, publications and lectures on digital pathology, images analysis, cytopathology and bone and soft tissue pathology.
4360097006_C AVG_Signal Outline The current concepts of digital pathology The practical applications of digital pathology in cytology Whole slide image cytology case interactive discussion Conclusions Gene Expression: RDES Drug Combo vs RDES No Drug by Avg_Signal 20000 10000 0 0 10000 20000 30000 4360097003_K AVG_Signal
Digital Pathology Definition An image-based information environment enabled by computer technology which allows for the management of information to be generated from a digital slide. Digital pathology is enabled in part by digital microscope, which is the practice of converting glass slides into digital slides that can be viewed, managed, and analyzed on a computer monitor. With the advent of Whole-Slide Imaging (WSI), the field of digital pathology has exploded and is currently regarded as one of the most promising avenues of diagnostic medicine in order to achieve even better, faster and cheaper diagnosis, prognosis and prediction of cancer and other important diseases.
Digital Pathology Environment Scan View Analyze Manage Integrate Share
Digital Pathology Potential The tissue on those slides may be subjected to staining to highlight structures. When those slides are digitalized, they then have the potential to be numerically analyzed using computer algorithms (image analysis). Algorithms can be used to automate the manual counting of structures, or for classifying the condition of tissue, like algorithms used in grading tumors. This could reduce human error and improve accuracy of diagnoses. Digital slides are also, by nature, easier to share than physical slides. This increases the potential of using data for education and consultations.
Digital Pathology Drivers Shortage of pathologists Remote access (telepathology) Consolidation of health systems, hospitals and laboratories due to accountable care organizations (ACOS) Total Accountable Care Organizations in US Source: HealthAffairsBlog by David Muhlestin and Mark McClellan April 21, 2016
Drivers
Digital Pathology Challenges Digital pathology is not yet approved by the FDA for primary diagnosis. Collaborating for down-classification: An update on the Digital Pathology Association's regulatory efforts Posted by Mike Montalto, PhD, Senior President-Elect of Digital Pathology Association (DPA) and is on DPA website https://digitalpathologyassociation.org/ Unlike digital radiology where the elimination of film made return on investment (ROI) clear, the ROI on digital pathology equipment is less obvious. The strongest ROI justification includes improved quality of healthcare, increased efficiency for pathologists, improved accessibility to expertises, and reduced costs in handling glass slides.
4360097006_C AVG_Signal Outline The current concepts of digital pathology The practical applications of digital pathology in cytopathology Whole slide image cytology case interactive discussion Conclusion Gene Expression: RDES Drug Combo vs RDES No Drug by Avg_Signal 20000 10000 0 0 10000 20000 30000 4360097003_K AVG_Signal
Digital Pathology Utility Courtesy of Dr. Eric Glassy
What is unique about cytology? Surgical vs. cytology slide a. Surgical slide 4-6 µm in thickness. b. Cytology slide 30 µm in thickness from glass to coverslip with cells positioned anywhere. Lee RE, et al: Evaluation and optimization for liquidbased preparation of cytology in whole slide imaging. J Pathol Inform. 2011: 2:46 Cytopathologists and cytotechnologists Screening, dotting and ergonomic issues Rapid On-Site Evaluation (ROSE) and telecytology GYN PAP smear and automated analysis
Are we ready? Literature on usage of whole-slide images (WSI) in clinical cytology diagnostic application, especially for primary diagnosis, is limited We studied the concordance in primary diagnosis between glass and digital (virtual) slides among diagnosticians with different training profiles to assess our readiness in adoption of digital cytology in clinical practice House J Bui MM, et al. Diagnostic digital cytopathology: are we ready yet? J Pathol Informatics 2013; 4: 28.
Method Digitized 22 de-identified routine cytology cases using Aperio ScanScope XT slide scanner At 20X/NAA 0.75 and 40x (with optical doubler) Image resolution: 0.5 µm per pixel at 20X or 0.25 µm per pixel at 40X Captured in single planes without z-stating or milti-plane imaging Positive 10 Negative 8 Other 4 Images viewed through Spectrum and Imagescope via intranet CPU Speed: 500MHz, 2GHz recommended Hard Drive: 100MB free space Memory: 256MB, 1GB recommended Network Card: 100 megabit network card or faster Video Card: 24-bit color at monitor s resolution OS: Windows XP Pro (SP2) or Windows Vista Pro
Method Diagnosticians: Cytopathologist with Digital Slide Experience 3 Cytopathologist with no Digital Slide Experience 3 Cytotechnologist 4 Pathology Resident 2 Gold standard: The reference glass slide diagnosis. Comparison: The glass and digital reading of the same diagnostician and among the 4 different groups in time and accuracy
We are ready!
How about the technology? WSI should not yet replace glass slides and microscopes in primary diagnosis because WSI has added cost, time, and underperformance in certain areas Challenges are in technology, such as 40X with optical doubler and focus electronically does not gain in resolution Limited by engineering issues of WSI image capture and viewing, such as faster speed, better screening and navigation tool, and better quality of digital slides Cytology WSI imaging application will dramatically increase when technical/engineering issues are resolved House J Bui MM, et al. Diagnostic digital cytopathology: are we ready yet? J Pathol Inf 2013; 4: 28. Technical requirement specific for digital cytopathology High resolution and speed 3D imaging and real time viewing Screening, dotting and ergonomic issues Data management and automated analysis
3D cell groups The three-dimensional coordinates shown demonstrate how the cluster of cells can be examined in the horizontal (X and Y) axis and/or the vertical (Z) axis. X A ThinPrep Pap test is shown of melanoma involving the cervix. The large 3D group of tumor cells in the middle is out of focus in the scanned plane of this digital image. DIAGNOSTIC HISTOPATHOLOGY 20:12
Solution to 3D cell groups
Multilayer stack vs. extended focus
WSI Scanner with Z-stacking
Z-stack WSI without scanning
Navigation, screening and annotation Search maps are shown for cytotechnologists at low, medium and high magnification of (a) a FNA smear and (b) ThinPrep slide. The light green area represents the examined area covered by the user. DIAGNOSTIC HISTOPATHOLOGY 20:12
ROSE and telecytopathology
Need & Opportunities MINI-SYMPOSIUM: WHOLE-SLIDE IMAGING IN PATHOLOGY DIAGNOSTIC HISTOPATHOLOGY 20:12
Need & Opportunities
4360097006_C AVG_Signal Outline The current concepts of digital pathology The practical applications of digital pathology in cytology Whole slide image cytology case interactive discussion Conclusion Gene Expression: RDES Drug Combo vs RDES No Drug by Avg_Signal 20000 10000 0 0 10000 20000 30000 4360097003_K AVG_Signal
4360097006_C AVG_Signal Whole Slides Images Case #1: Meningioma in a patient with history of breast cancer Case #2: Intraductal papillary mucinous neoplasm in a patient with a cystic mass of tail of pancreas and dilated main pancreatic duct Case #3: Solid-pseudopapillary neoplasm of pancreas Gene Expression: RDES Drug Combo vs RDES No Drug by Avg_Signal 20000 10000 0 0 10000 20000 30000 4360097003_K AVG_Signal
4360097006_C AVG_Signal Outline The current concepts of digital pathology The practical applications of digital pathology in cytology Whole slide image cytology case interactive discussion Conclusion: Pathologists are leaders in the changing world of precision medicine Gene Expression: RDES Drug Combo vs RDES No Drug by Avg_Signal 20000 10000 0 0 10000 20000 30000 4360097003_K AVG_Signal
Accurate pathologic diagnosis is essential to ensure the most effective treatment
Value of a Pathologist Pathologists working in partnership with a clinical team can generate as much as 30% of system value, while lab testing represents only 3% of system costs 70% of medical decisions made by physicians are based on lab findings Pathologists can help physician practices effectively manage their patients by: - Patient registry and laboratory data management - Interpretation of lab tests and clinical decision-making - Patient education and empowerment 2011 College of American Pathologists. All rights reserved.
A patient s medical journey begins with their diagnosis Courtesy of Dr. Mark Lloyd we provide forecast of Diagnosis Prognosis Therapeutic selection and prediction
Pathologists are Leaders in Precision Medicine Uniquely qualified to determine the clinical value of complex (and costly) tests Uniquely qualified to interpret the results of genomic and other molecular tests that can predict a patient s predisposition toward a disease, and yield better results in managing a disease At the forefront of advancing personalized medicine with new methods of molecular and genetic analysis for disease diagnosis and management 2011 College of American Pathologists. All rights reserved.
Bright Future of Digital Pathology Disruptive technologies are emerging which will impact clinical diagnostics Genomics Circulating tumor cells and liquid biopsy Digital pathology and image analysis These applications will transform Anatomic Pathology We must embrace the future with collaborative mentality
CAP Digital Pathology Committee Charge To advance the adoption of digital pathology within the CAP and to serve as a respected resource for information and education for pathologists, patients and the public on the practice and science of digital pathology.
CAP and Other Pathology Societies Guidelines
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